Controlled release tablet containing water soluble medicament

Abstract

A sustained or controlled release tablet is disclosed. The tablet comprises a water soluble medicament, a hydroxypropyl methylcellulose having sustaining action, a pharmaceutical binding agent, and a hydrophobic component.

We claim: 
     
       1. A controlled release uncoated tablet comprising: (a) about 5-20 percent by weight hydroxypropyl methylcellulose having a viscosity of about 1000 or greater, a substitution rate for the methoxyl group of about 7-30% and a substitution rate for the hydroxypropoxyl group of about 7-20%;   (b) about 2-8 percent by weight hydroxypropyl methylcellulose having a viscosity of less than about 1000, methyl cellulose, or polyvinyl pyrollidone;   (c) about 5-15 percent by weight hydrogenated vegetable oil or stearic acid; and   (d) a therapeutically active material having a water solubility of about 0.1-30% at normal room temperature;   wherein said tablet has a dissolution profile, with a substantially zero order absorption characteristic, of about 10-35% within 2 hours after ingestion.   
     
     
       2. A controlled release uncoated tablet comprising: (a) about 5-30 percent by weight hydroxypropyl methylcellulose with sustaining properties;   (b) about 2-15 percent by weight water soluble pharmaceutical binder;   (c) about 2-20 percent by weight hydrophobic component; and   (d) a medicament having a solubility of about 0.1 to 30 wt-% in water; wherein said tablet has a dissolution profile, with a substantially zero order absorption characteristic, of about 10-35% within 2 hours after ingestion.     
     
     
       3. The controlled release tablet of claim 2 wherein the water soluble medicament comprises niacin and forms about 50-85 percent by weight of the tablet. 
     
     
       4. The controlled release tablet of claim 2 wherein the hydroxypropyl methylcellulose comprises a hydroxypropyl methylcellulose having a nominal viscosity, 2 percent aqueous solution, of about 100,000 cps, a methoxyl content of about 19-24 percent, a hydroxypropoxyl content of about 7-12 percent, and a particle size where at least 90 percent passes through a USS 100 mesh screen. 
     
     
       5. The controlled release tablet of claim 2 wherein the water soluble pharmaceutical binder is selected from the group consisting of hydroxypropyl methylcellulose having binding properties, polyvinyl pyrollidone, methyl cellulose, gelatin, starch, sucrose, and lactose. 
     
     
       6. The controlled release tablet of claim 5 wherein the water soluble pharmaceutical binder comprises hydroxypropyl methylcellulose having binding properties. 
     
     
       7. The controlled release tablet of claim 5 wherein the water soluble pharmaceutical binder comprises polyvinyl pyrollidone. 
     
     
       8. The controlled release tablet of claim 6 wherein the hydroxypropyl methylcellulose having binding properties comprises hydroxypropyl methylcellulose having a nominal viscosity, 2 percent aqueous solution, of about 15 cps, a methoxy content of about 28-30 percent, a hydroxypropoxyl content of about 7-12 percent, and a particle size of 100% through a USS No. 30 mesh screen and 99% through a USS No. 40 mesh screen. 
     
     
       9. The controlled release tablet of claim 2 wherein the hydrophobic component comprises a wax-like insoluble material. 
     
     
       10. The controlled release tablet of claim 9 wherein the wax-like insoluble material is selected from the group consisting of hydrogenated vegetable oil and stearic acid. 
     
     
       11. The controlled release tablet of claim 10 wherein the wax-like insoluble material comprises a hydrogenated vegetable oil, the hydrogenated vegetable oil comprising a triglyceride of stearic acid. 
     
     
       12. The controlled release tablet of claim 2 further comprising up to about 5 percent by weight external lubricant. 
     
     
       13. The controlled release tablet of claim 12 wherein the external lubricant comprising glyceryl behenate. 
     
     
       14. The controlled release tablet of claim 13 wherein the external lubricant further comprises magnesium stearate. 
     
     
       15. The controlled release tablet of claim 2 wherein the hydroxypropyl methylcellulose with sustaining properties forms about 5-20 percent by weight of the tablet, the water soluble pharmaceutical binder forms about 2-8 percent by weight of the tablet, and the hydrophobic component forms about 5-15 percent by weight of the tablet. 
     
     
       16. The controlled release tablet of claim 3 wherein the percentage of niacin released in the 2 hours following following ingestion of the tablet is about 10-30 percent by weight. 
     
     
       17. The controlled release tablet of claim 3 wherein the percentage of the niacin released in the 8 hours following ingestion of the tablet is about 40-70 percent by weight. 
     
     
       18. The controlled release tablet of claim 17 wherein at least 90% release of the niacin occurs within 24 hours following ingestion of the tablet. 
     
     
       19. The controlled release tablet of claim 2 wherein the tablet is readily divisible into portions, each portion forming a smaller dose than the dose of the intact tablet. 
     
     
       20. The controlled release tablet of claim 3 wherein the tablet contains about 250 milligrams of niacin. 
     
     
       21. The controlled release tablet of claim 3 wherein the tablet contains about 500 milligrams of niacin. 
     
     
       22. The controlled release tablet of claim 3 wherein the tablet contains about 750 milligrams of niacin. 
     
     
       23. The controlled release tablet of claim 1 wherein the therapeutically active material forms from about 30-90% by weight of the tablet. 
     
     
       24. The controlled release tablet of claim 1 wherein the therapeutically active compound comprises niacin and forms from about 50-85 percent by weight of the tablet.